Many Indigenous peoples are reliant on natural resources for their economic, cultural, and physical well-being and are often uniquely affected by climate change. The impacts of climate change on water, land, coastal areas, and other natural resources, as well as infrastructure and related services, are expected to increasingly disrupt Indigenous peoples’ livelihoods and economies, including agriculture and agroforestry, fishing, recreation, and tourism. Adverse impacts on subsistence activities have already been observed. As climate changes continue, adverse impacts on culturally significant species and resources are expected to result in negative physical and mental health effects. Throughout the United States, climate-related impacts are causing some Indigenous peoples to consider or actively pursue community relocation as an adaptation strategy, presenting challenges associated with maintaining cultural and community continuity. While economic, political, and infrastructure limitations may affect these communities’ ability to adapt, tightly knit social and cultural networks present opportunities to build community capacity and increase resilience. Many Indigenous peoples are taking steps to adapt to climate change impacts structured around self-determination and traditional knowledge, and some tribes are pursuing mitigation actions through development of renewable energy on tribal lands.